Division of Hematology, Department of Internal Medicine, Cancer Center, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
Oncogene. 2011 Mar 3;30(9):1009-19. doi: 10.1038/onc.2010.511. Epub 2010 Nov 15.
Accumulating evidence indicates that many human cancers are organized as a cellular hierarchy initiated and maintained by self-renewing cancer stem cells. This cancer stem cell model has been most conclusively established for human acute myeloid leukemia (AML), although controversies still exist regarding the identity of human AML stem cells (leukemia stem cell (LSC)). A major implication of this model is that, in order to eradicate the cancer and cure the patient, the cancer stem cells must be eliminated. Monoclonal antibodies have emerged as effective targeted therapies for the treatment of a number of human malignancies and, given their target antigen specificity and generally minimal toxicity, are well positioned as cancer stem cell-targeting therapies. One strategy for the development of monoclonal antibodies targeting human AML stem cells involves first identifying cell surface antigens preferentially expressed on AML LSC compared with normal hematopoietic stem cells. In recent years, a number of such antigens have been identified, including CD123, CD44, CLL-1, CD96, CD47, CD32, and CD25. Moreover, monoclonal antibodies targeting CD44, CD123, and CD47 have demonstrated efficacy against AML LSC in xenotransplantation models. Hopefully, these antibodies will ultimately prove to be effective in the treatment of human AML.
越来越多的证据表明，许多人类癌症是由自我更新的癌症干细胞启动和维持的细胞层级结构组成的。这个癌症干细胞模型在人类急性髓细胞白血病（AML）中得到了最确凿的证实，尽管关于人类 AML 干细胞（白血病干细胞（LSC））的身份仍存在争议。该模型的一个主要含义是，为了消除癌症并治愈患者，必须消除癌症干细胞。单克隆抗体已成为治疗多种人类恶性肿瘤的有效靶向治疗方法，鉴于其靶抗原特异性和一般最小毒性，它们非常适合作为癌症干细胞靶向治疗方法。开发针对人类 AML 干细胞的单克隆抗体的一种策略涉及首先鉴定与正常造血干细胞相比优先在 AML LSC 上表达的细胞表面抗原。近年来，已经鉴定出许多这样的抗原，包括 CD123、CD44、CLL-1、CD96、CD47、CD32 和 CD25。此外，针对 CD44、CD123 和 CD47 的单克隆抗体在异种移植模型中已被证明对 AML LSC 有效。希望这些抗体最终能在治疗人类 AML 中证明是有效的。
